By Crystal Phend, Senior Staff Writer, MedPage Today
Published: June 21, 2010
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of Medicine, Harvard Medical School, Boston and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
Although the liver is often overlooked in diabetes, even newly-diagnosed cases carry a substantial risk of serious hepatic damage, researchers found.
In a population-based study, newly-diagnosed diabetes was associated with a near doubling in the rate of liver cirrhosis, liver failure, or liver transplant compared with people in the general population who did not have diabetes, according to Gillian Booth, MD, MSc, of St. Michael's Hospital in Toronto, and colleagues.
After adjusting for important contributors to liver disease, the association remained significant with a 77% increased risk for newly-diagnosed diabetes patients (95% confidence interval 68% to 86%), they reported online in CMAJ.Action Points
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Note that the retrospective study could not determine whether diabetes caused the liver disease seen during follow-up.
Note that diabetes guidelines do not recommend screening for liver disease.
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"The negative impact of diabetes on the retinal, renal, nervous, and cardiovascular systems is well recognized, yet little is known about its effect on the liver," they wrote.
Although much still remains to be discovered about the mechanisms and cause of the link between diabetes and liver disease, nonalcoholic steatohepatitis (NASH) is almost certainly involved, according to Kenneth Cusi, MD, who has been studying this condition at the University of Texas Health Science Center in San Antonio.
Steatosis is known to arise in relationship to insulin resistance in obesity, and most people with the condition do have some degree of glucose abnormality, he explained in an interview.
The two seem to "feed on each other," Cusi said.
Unlike with eye disease, cardiovascular disease, and kidney disease, guidelines for diabetes care don't recommend screening for liver disease.
"However, when the liver fails," Booth's group cautioned in the paper, "there is no equivalent form of management, such as hemodialysis or retinal photocoagulation."
They suggested that liver disease "may be appropriate for addition to the list of target-organ conditions related to diabetes," with annual screening by means of a blood test, such as for the liver enzyme alanine aminotransferase.
But the sensitivity of blood tests and even ultrasound aren't great for identifying fatty liver disease that is the precursor to more serious liver problems and liver biopsy is not a feasible screening method, Cusi noted.
Also, it would first have to be shown that preventive measures such as weight loss and glycemic and lipid control are effective in diabetes, as they are in isolated fatty liver without diabetes, the researchers said.
To expand evidence for the link, the researchers retrospectively examined the administrative databases of the universal healthcare system in the province of Ontario from 1994 through 2006.
They compared 438,069 adults with newly diagnosed diabetes and an age-, sex-, and regionally-matched control group of 2,059,708 individuals without known diabetes. Preexisting liver or alcohol-related disease were cause for exclusion.
During a median of 6.4 years of follow-up, serious liver disease -- liver cirrhosis, liver failure, or liver transplant -- developed in 2,463 newly-diagnosed diabetes cases and 5,902 controls.
Thus, unadjusted liver disease incidence was 92% higher with diabetes (8.19 per 10,000 person-years with diabetes and 4.17 without it).
This difference remained significant across mutually-adjusted patient subgroups by age, gender, urban versus rural residence, and income level.
Diabetes appeared to have the most pronounced link with liver cirrhosis (adjusted hazard ratio 2.55, 95% CI 2.35 to 2.76) and the least with liver transplantation (adjusted HR 1.31, 95% CI 1.05 to 1.64).
Hypertension and obesity didn't appear to entirely account for the relationship with diabetes. The risk of serious liver disease in nondiabetic individuals with preexisting hypertension or obesity was elevated but less so than among those with diabetes.
But the researchers cautioned that it is difficult to separate out the effects of these related conditions.
"Although our findings and those of the U.S. study [which found elevated chronic NASH risk in veterans with diabetes] edge forward the idea that diabetes may be harmful to the liver, the question remains of whether this effect extends beyond the metabolic syndrome," they wrote.
Another question that remains to be answered is causality.
Booth's group pointed out that hepatic fat content rises in parallel with insulin resistance and glucose dysregulation and that diabetes as a complication of cirrhosis typically doesn't arise until cirrhosis reaches an advanced stage.
However, they noted, they couldn't rule out the pre-existence of subclinical liver disease before study entry.
The study was funded by the Banting and Best Diabetes Centre at the University of Toronto and by the Institute for Clinical Evaluative Sciences, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care
The researchers reported no conflicts of interest.
Cusi reported support from the American Diabetes Association and the Boris Welcome Fund and an award from the VA. Takeda provided the study drug for research he is doing in NASH but no personal renumeration to Cusi.
Primary source: CMAJ
Source reference:
Porepa L, et al "Newly diagnosed diabetes mellitus as a risk factor for serious liver disease" CMAJ 2010
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